This proposal extends the Phase I study that demonstrated the feasibility of applying newly developed cloning vectors for the generation of large random peptide libraries. These hybrid vectors, combined with the power of phage genetics and combinatorial in vivo cloning, will permit the synthesis and analysis of all possible permutations of amino acids comprising peptides up to 12 residues in length. This goal requires that libraries of up to 1 x 10 (15) members be generated, and represents an improvement over existing efficiencies by at least 4 orders of magnitude. Through biopanning of these peptides expressed on the surface of phage particle it is possible to recover and identify peptides that interact with specific legands, receptors, substrates, antigens, and antibodies. The system described in this proposal offers tremendous potential for identifying valuable peptides for therapeutic, diagnostic, and catalytic uses. The overall market potential for such system approaches that available for monoclonal antibodies. In addition, there exists an opportunity for improving existing protein modeling and engineering strategies.